A rat-based preclinical platform facilitating transcatheter hepatic arterial infusion in immunodeficient rats with liver xenografts of patient-derived pancreatic ductal adenocarcinoma.

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens underwent histopathological examination. A liver-implanted PDAC PDX rat model was established in all 63 rats, with first CT identifying all tumors. Four weeks post-treatment, arterial infusion groups exhibited significantly smaller tumor volumes than controls for all three tumors on second CT. Xenograft tumors histologically maintained adenocarcinoma features compared to original patient tumors. Ki67 expression was significantly lower in arterial infusion groups than in the other two for the three tumors, indicating reduced tumor growth in PDX rats. A liver-implanted PDAC PDX rat model was established as a rat-based preclinical platform. Arterial cisplatin infusion chemotherapy represents a potential therapy for PDAC liver metastasis.

Screening of aspiration pneumonia using the modified Mallampati classification tool in older adults.

Pneumonia is a major cause of morbidity and mortality in older adults. In the aging society, screening methods for predicting aspiration pneumonia are crucial for its prevention. Changes in the oropharyngeal morphology and hyoid bone position may increase the risk of aspiration pneumonia. This multicenter study aimed to investigate a simple and effective screening method for predicting dysphagia and aspiration pneumonia. Overall, 191 older adults (aged 65 years or older) were randomly sampled using the simple random sampling technique. Oropharyngeal morphology was assessed using the modified Mallampati classification, which reflects the size of the tongue in the oropharyngeal cavity. The hyoid position was measured as the distance between the menton and laryngeal prominence to evaluate aging-related changes in the muscles of the laryngopharynx. Dysphagia was assessed using the repetitive saliva swallowing test (RSST), which measures the number of swallowing movements in 30 seconds; dysphasia is defined as less than 3 swallowing movements in 30 seconds. The aspiration signs were assessed based on history of choking or coughing reflex during eating or drinking and medical history of pneumonia. The study findings revealed that the modified Mallampati classification was significantly correlated with a medical history of pneumonia. A higher incidence of pneumonia was evident in the lower Mallampati classification, which shows the smaller size of the tongue base in the oropharyngeal cavity. The results of this study suggest that the modified Mallampati classification may be a possible screening method to predict the occurrence of pneumonia.

Percutaneous transhepatic sclerotherapy for ascending colonic varices due to left-sided portal hypertension.

Left-sided portal hypertension (LSPH) causes varices and splenomegaly due to splenic vein issues. Colonic varices are rare and lack standardized treatment. We report the successful treatment of colonic varices caused by LSPH, by addressing both the afferent and efferent veins. A 70-year-old man with distal cholangiocarcinoma had surgery without splenic vein resection, leading to proximal splenic vein stenosis and varices at multiple locations. Percutaneous transhepatic splenic venography revealed that collateral veins flowed into the ascending colonic varices and returned to the portal vein. Complete thrombosis of the varices was achieved by injecting sclerosants and placing coils in both the afferent and efferent veins. The procedure was safe and effective, with no variceal recurrence. This approach provides a minimally invasive option for treating colonic varices associated with LSPH.

Wood cauliflower mushroom (Sparassis crispa) suppresses the body weight and visceral fat increased by ovariectomy in mice.

Sparassis crispa, an edible mushroom, has been reported to show many kinds of physiological functions. The present paper focused on reducing body weight, subcutaneous fat, and visceral fat gain in ovariectomized (OVX) mice. Using the fruiting body powder of the indoor cultivation S. crispa (IT S. crispa: ITSc), one week after the OVX, ITSc was administered to two OVX groups by per os (p.o). In the sham group, 10 mL/kg water and 10 mL/kg saline were administered by p.o. and subcutaneous adm, respectively. OVX groups were divided into four groups. These treatments were performed on animals 6 days a week for 8 weeks. Subcutaneous and visceral fat measurements were performed under inhalation anesthesia with isoflurane using a Latheta LCT-200 X-ray CT system. The biochemical markers and the mRNA expression levels of the PPARγ, adiponectin, TNF-α, PPARα, and leptin were measured. Significant increases in body weight, fat ratio, and glucose levels were detected in OVX mice compared to sham mice. These increases were significantly blocked by ITSc, but not estradiol. Furthermore, ITSc treatment significantly increased adiponectin and leptin levels in adipose tissue. These results suggest that ITSc improves lipid abnormalities due to the less activity of women's ovary function, excluding estrogen functions.

Contrasting Roles of Programmed Death-Ligand 1 Expression in Tumor and Stroma in Prognosis of Esophageal Squamous Cell Carcinoma.

The assessment of programmed death-ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) has become increasingly important with the rise of immune checkpoint inhibitors (ICIs). However, challenges persist, including subjective interpretation and the unclear significance of staining intensity, as well as contrasting roles in tumoral and stromal regions. Our study enhances the understanding of PD-L1 in ESCCs by analyzing its expression in tumors and stroma with H-scores, highlighting its distinct clinicopathological impacts. In a retrospective cohort of 194 ESCC specimens from surgical resection, we quantified PD-L1 expression in tumoral and stromal compartments using H-scores, analyzing whole slide images with digital pathology analysis software. Kaplan-Meier analysis demonstrated that higher PD-L1 expression is significantly associated with improved postoperative overall survival (OS) and recurrence-free survival (RFS) in both tumoral and stromal areas. Multivariable analysis identified high tumoral PD-L1 expression as an independent prognostic factor for prolonged OS and RFS (HR = 0.47, p = 0.007; HR = 0.54, p = 0.022, respectively). In a separate analysis, high stromal PD-L1 expression was found to correlate with less advanced pathological stages and a prolonged response to cytotoxic chemotherapy, with no similar correlation found for ICI treatment response. This study reveals PD-L1's contrasting role in the ESCC tumor immune microenvironment, impacting prognosis, tumor stage, and treatment response.

Concurrent trastuzumab deruxtecan-induced interstitial lung disease and COVID-19 in the treatment of advanced breast cancer.

Patients with cancer are at an increased risk of developing coronavirus disease 2019 (COVID-19) infection. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) against epidermal growth factor receptor 2 (HER2)-positive cancer, known to cause drug-induced interstitial lung disease (DILD), including drug-induced pneumonitis. A 60-year-old woman with breast cancer developed a fever during treatment with T-DXd and was diagnosed with COVID-19. The fever persisted for approximately 3 weeks, and chest computed tomography showed multiple consolidations with bilateral peripheral predominance. Since the clinical course was atypical for COVID-19 due to the long duration of the fever and the CT pattern was frequently seen in T-DXd-induced ILD, the patient was diagnosed with T-DXd-induced ILD, following which, prednisolone was started, leading to improvement in the symptoms and fading of shadows. Even in patients suspected of COVID-19 pneumonia, physicians should consider the possibility of DILD, particularly in patients undergoing cancer treatment.

Clitoral preputial edema can be mistaken for clitoromegaly: a clinical analysis of ten cases.

Background and objectives: We herein reported ten, female neonates with transient clitoral preputial edema, which was mistaken for clitoromegaly. Although it is well known that the clitoris is prominent in premature, female neonates, there are as of yet no reports of clitoral preputial edema in full-term neonates. The present study was conducted to clarify the clinical course of clitoral preputial edema. Methods: Seventeen, Japanese patients aged < 6 months with suspected clitoromegaly were enrolled, and their clinical course was analyzed retrospectively. Clitoral preputial edema was defined by 1) a normal clitoral glans despite edema; and 2) the absence of established differences of sexual development, such as 21-hydroxylase deficiency. Results: Ten of the 17 patients with suspected clitoromegaly had clitoral preputial edema; eight of the ten patients were full-term, and the remaining two were preterm neonates. The median age at the first visit was 8 days. Edema of the labia minora and labia majora, rugosity of the labia majora, and hymenal polyps often accompanied the clitoral preputial edema. Seven patients were examined at our division during the neonatal period, and three patients were examined in the post-neonatal period. Age at reduction of the clitoral width to < 7 mm ranged from 8 to 74 days in four of the seven neonatal patients. In the three post-neonatal patients, age to reduction in the clitoral width ranged from 107 to 243 days. Conclusions: Transient clitoral preputial edema is often mistaken for clitoromegaly. The key to diagnosing clitoral preputial edema lies in its characteristic appearance and improvement course.

Generalizable neuromarker for autism spectrum disorder across imaging sites and developmental stages: A multi-site study.

Autism spectrum disorder (ASD) is a lifelong condition, and its underlying biological mechanisms remain elusive. The complexity of various factors, including inter-site and development-related differences, makes it challenging to develop generalizable neuroimaging-based biomarkers for ASD. This study used a large-scale, multi-site dataset of 730 Japanese adults to develop a generalizable neuromarker for ASD across independent sites and different developmental stages. Our adult ASD neuromarker achieved successful generalization for the US and Belgium adults and Japanese adults. The neuromarker demonstrated significant generalization for children and adolescents. We identified 141 functional connections (FCs) important for discriminating individuals with ASD from TDCs. Finally, we mapped schizophrenia (SCZ) and major depressive disorder (MDD) onto the biological axis defined by the neuromarker and explored the biological continuity of ASD with SCZ and MDD. We observed that SCZ, but not MDD, was located proximate to ASD on the biological dimension defined by the ASD neuromarker. The successful generalization in multifarious datasets and the observed relations of ASD with SCZ on the biological dimensions provide new insights for a deeper understanding of ASD.

Deep Infantile Hemangioma in the Involuting Phase That Was Difficult to Diagnose before Surgery.

Infantile hemangioma (IH) is a common pediatric vascular tumor and is easily diagnosed in most cases based on the clinical course and appearance, but deep IHs are difficult to diagnose based on external appearance alone. Clinical and imaging findings are therefore important clues to the diagnosis of soft tissue tumors; however, a definitive diagnosis is decided based on the pathological examination of biopsy or resection specimens. A 1-year-old girl with a subcutaneous mass on her glabella was referred to our hospital. At 3 months of age, her mother noticed a tumor that swelled when she cried. It gradually enlarged, and ultrasonography and magnetic resonance imaging were performed at 12 months of age. Doppler ultrasonography showed a hypo-vascular mass. Magnetic resonance imaging revealed a subcutaneous mass with low-intensity on T1-weighted image and slightly high-intensity on T2-weighted image, with tiny flow voids. Computed tomography showed no frontal bone defect. The soft tissue tumor could not be diagnosed based on these imaging findings; thus, we decided to perform total resection under general anesthesia. A histopathological examination showed a highly cellular tumor with capillaries with opened small vascular channels and glucose transporter 1 positivity. Thus, it was diagnosed as deep IH transitioning from the proliferative phase to the involuting phase. Deep IHs are difficult to diagnose because characteristic imaging findings disappear during the involuting phase. We emphasize the importance of performing Doppler ultrasonography in the early phase (eg, at 6 months of age) for soft tissue tumors of infancy.

Generalizable neuromarker for autism spectrum disorder across imaging sites and developmental stages: A multi-site study.

Autism spectrum disorder (ASD) is a lifelong condition, and its underlying biological mechanisms remain elusive. The complexity of various factors, including inter-site and development-related differences, makes it challenging to develop generalizable neuroimaging-based biomarkers for ASD. This study used a large-scale, multi-site dataset of 730 Japanese adults to develop a generalizable neuromarker for ASD across independent sites (U.S., Belgium, and Japan) and different developmental stages (children and adolescents). Our adult ASD neuromarker achieved successful generalization for the US and Belgium adults (area under the curve [AUC] = 0.70) and Japanese adults (AUC = 0.81). The neuromarker demonstrated significant generalization for children (AUC = 0.66) and adolescents (AUC = 0.71; all P<0.05, family-wise-error corrected). We identified 141 functional connections (FCs) important for discriminating individuals with ASD from TDCs. These FCs largely centered on social brain regions such as the amygdala, hippocampus, dorsomedial and ventromedial prefrontal cortices, and temporal cortices. Finally, we mapped schizophrenia (SCZ) and major depressive disorder (MDD) onto the biological axis defined by the neuromarker and explored the biological continuity of ASD with SCZ and MDD. We observed that SCZ, but not MDD, was located proximate to ASD on the biological dimension defined by the ASD neuromarker. The successful generalization in multifarious datasets and the observed relations of ASD with SCZ on the biological dimensions provide new insights for a deeper understanding of ASD.

Precision Mapping of Thalamic Deep Brain Stimulation Lead Positions Associated With the Microlesion Effect in Tourette Syndrome.

BACKGROUND: The microlesion effect refers to the improvement of clinical symptoms after deep brain stimulation (DBS) lead placement and is suggested to indicate optimal lead placement. Very few studies have reported its implications in neuropsychiatric disorders. OBJECTIVE: To evaluate the magnitude of the microlesion effect in Tourette syndrome and the relationship between the microlesion effect and the anatomic location of implanted DBS leads. METHODS: Six male patients were included. Their median age at surgery and follow-up period were 25 years (range, 18-47) and 12 months (range, 6-24), respectively. All patients were videotaped pre- and postoperatively, and tic frequencies were counted. We also analyzed the precision of lead placement and evaluated the normative connectome associated with the microlesion area. RESULTS: The microlesion effect was observed as an improvement in tic symptoms in all patients, and the long-term clinical outcomes were favorable. The median motor tic frequency was 20.2 tics/min (range, 9.7-60) at baseline and decreased to 3.2 tics/min (1.2-11.3) in patients on postoperative day 1 ( P = .043) and to 5.7 tics/min (range, 1.9-16.6) in patients on postoperative day 7 ( P = .028). Phonic tic tended to improve immediately after surgery although the changes were not significant. Image analyses revealed that the precise position of the electrode was directed toward the anteromedial centromedian nucleus. Normative connectome analysis demonstrated connections between improvement-related areas and wide areas of the prefrontal cortex. CONCLUSION: This study shows that the microlesion effect may seem as an immediate improvement after optimal DBS lead placement in patients with Tourette syndrome.

Physiologic 18F-FDG muscle uptake in severe COPD: Implications for accurate lung cancer staging.

Recognizing physiologic 18F-fluorodeoxyglucose (FDG) uptake in severe COPD is crucial to avoid mistaking it for lung cancer metastasis. Correlating 18F-FDG avid lesions with co-registered computed tomography is essential for accurate lung cancer staging and preventing unnecessary interventions.

[Possible Radiation Dose Reduction in Abdominal Plain CT Using Deep Learning Reconstruction].

PURPOSE: The purposes of this study were to evaluate the low-contrast detectability of CT images assuming hepatocellular carcinoma and to determine whether dose reduction in abdominal plain CT imaging is possible. METHODS: A Catphan 600 was imaged at 350, 250, 150, and 50 mA using an Aquilion ONE PRISM Edition (Canon) and reconstructed using deep learning reconstruction (DLR) and model-based iterative reconstruction (MBIR). A low-contrast object-specific contrast-to-noise ratio (CNRLO) was measured and compared in a 5-mm module with a CT value difference of 10 HU, assuming hepatocellular carcinoma; a visual examination was also performed. Moreover, an NPS within a uniform module was measured. RESULTS: CNRLO was higher for DLR at all doses (1.12 at 150 mA for DLR and 1.07 at 250 mA for MBIR). On visual evaluation, DLR could detect up to 150 mA and MBIR up to 250 mA. The NPS was lower for DLR at 0.1 cycles/mm at 150 mA. CONCLUSION: The low-contrast detection performance was better with DLR than with MBIR, indicating the possibility of dose reduction.

Transient asymptomatic pulmonary opacities in a patient with MET exon 14 skipping non-small cell lung cancer: A case report.

Mesenchymal epithelial transition factor receptor (MET) tyrosine kinase inhibitors (MET-TKIs) have been approved for the treatment of non-small cell lung cancers with MET exon 14 skipping mutations. Transient asymptomatic pulmonary opacities (TAPOs) associated with epidermal growth factor receptor (EGFR)-TKIs have been reported. Here, we report a case wherein ground-glass opacities (GGOs) appeared during the course of treatment with tepotinib, a MET-TKI, but spontaneously resolved with drug withdrawal, after which treatment was resumed with a reduced dose. Although there have been no reports of TAPOs with MET-TKIs, the clinical and imaging findings of this case were consistent with TAPOs. For TAPOs occurring because of MET-TKI, the drug can be continued under careful observation even if GGOs appear.

Impallidane skeleton as a novel triterpenoid methyl ether from rhizomes of Imperata cylindrica var. koenigii f. pallida.

ABSTRUCT: n-Hexane extract of rhizomes of Imperata cylindrica var. koenigii f. pallida yielded five novel skeletal triterpenoids, designed as impallidin (1), impallidol (2), impallidin ozonide (3a, 3b), trisnorimpallidin aldehyde (4), tetranorimpallidin aldehyde (5). Structures of novel compounds were elucidated by mainly 2D NMR and other spectroscopic analysis and chemical correlations. Alternatively, compound 3a, 3b was derivatized from 1 under ozone oxidation condition.

Quality of life of patients with hematological malignancies and factors affecting health state utility values.

PURPOSE: It is well studied that physical function and social background affect the quality of life (QoL) of cancer patients. However, differences in QoL by age and factors affecting health state utility values (HSUV) of patients with hematological malignancies have not yet been sufficiently investigated. Our aim is to investigate the factors that affect QoL and HSUV in such patients. METHODS: A total of 32 patients with hematological malignancies on outpatient chemotherapy were included. QoL and HSUV were evaluated using the EuroQol-5 Dimension 5-level (EQ-5D-5L). Physical function was assessed using grip strength, knee extension strength, 6-min walking distance, and Short Physical Performance Battery (SPPB). Fatigue was assessed using Brief Fatigue Inventory (BFI), and nutritional status was assessed using Mini Nutritional Assessment-Short Form (MNA-SF). RESULTS: In the EQ-5D-5L, a high percentage of the patients were aware of mobility problems and pain/discomfort, and mobility problems were more common in the older-aged group (≥ 65 years old, n = 16) than in the middle-aged group (< 65 years old, n = 16). In addition, the older-aged group showed lower HSUV and physical function. SPPB (ß = 0.38, p < 0.01), BFI (ß = - 0.58, p < 0.01), and MNA-SF (ß = 0.29, p = 0.02) were independent factors affecting HSUV (adjusted R2 = 0.65, p < 0.01). BFI was correlated with HSUV in both older and middle-aged groups. CONCLUSION: Comprehensive supports, to improve lower extremity function, fatigue, and nutritional status, are required to augment QoL and HSUV in patients with hematological malignancies.

Low-radiation dose scan protocol for preoperative imaging for dental implant surgery using deep learning-based reconstruction in multidetector CT.

OBJECTIVES: This study aimed to investigate the impact of a deep learning-based reconstruction (DLR) technique on image quality and reduction of radiation exposure, and to propose a low-dose multidetector-row computed tomography (MDCT) scan protocol for preoperative imaging for dental implant surgery. METHODS: The PB-1 phantom and a Catphan phantom 600 were scanned using volumetric scanning with a 320-row MDCT scanner. All scans were performed with a tube voltage of 120 kV, and the tube current varied from 120 to 60 to 40 to 30 mA. Images of the mandible were reconstructed using DLR. Additionally, images acquired with the 120-mA protocol were reconstructed using filtered back projection as a reference. Two observers independently graded the image quality of the mandible images using a 4-point scale (4, superior to reference; 1, unacceptable). The system performance function (SPF) was calculated to comprehensively evaluate image quality. The Wilcoxon signed-rank test was employed for statistical analysis, with statistical significance set at p value < 0.05. RESULTS: There was no significant difference between the image quality acquired with the 40-mA tube current and reconstructed with the DLR technique (40DLR), and that acquired with the reference protocol (3.00, 3.00, p = 1.00). The SPF at 1.0 cycles/mm acquired with 40DLR was improved by 156.7% compared to that acquired with the reference protocol. CONCLUSIONS: Our proposed protocol, which achieves a two-thirds reduction in radiation dose, can provide a minimally invasive MDCT scan of acceptable image quality for dental implant surgery.

Clinical outcomes of 34 patients with resistance to thyroid hormone beta: a twenty-year experience in Japan.

Resistance to thyroid hormone beta (RTHß) caused by germline mutations in genes encoding thyroid hormone receptor beta (TRß) is a rare disorder. Little information is available regarding the clinical experience of this syndrome in Japan. We retrospectively reviewed the records of 34 patients with RTHß (21 adult females and 13 adult males) with positive TRß mutations identified at our division between 2000 and 2020. Of the 24 patients with available clinical history, 10 (41.7%) received inappropriate treatments such as antithyroid drugs, thyroidectomy, or radioactive iodine. Diagnostic delay and inappropriate management of RTHß are still present in Japan. Every patient except one demonstrated thyroid hormone profiles indicative of syndrome of inappropriate secretion of thyrotropin (SITSH), characterized by a hormonal profile of hyperthyroxinemia with a non-suppressed TSH concentration. Since the most common forms of hyperthyroidism including Graves' disease feature elevated thyroid hormone levels with suppressed TSH concentrations, early diagnosis of SITSH is critical for preventing inappropriate management. One patient positive for anti-thyroglobulin antibody (Tg-Ab) and anti-thyroperoxidase antibody (TPO-Ab) showed remarkably elevated TSH (>200 µIU/mL) despite thyroid hormone concentrations within the reference ranges. At least one thyroid autoantibody (Tg-Ab, TPO-Ab, or thyrotropin receptor antibodies) was identified in 37.9% (11/29) of the patients tested. One patient developed overt Graves' disease nine years after RTHß diagnosis. These findings suggest that RTHß is frequently comorbid with additional autoimmune thyroid disorders. Further research is required to identify the most appropriate treatments for RTHß patients who develop a second thyroid disorder.

Deep-learning reconstruction for ultra-low-dose lung CT: Volumetric measurement accuracy and reproducibility of artificial ground-glass nodules in a phantom study.

OBJECTIVES: The lung nodule volume determined by CT is used for nodule diagnoses and monitoring tumor responses to therapy. Increased image noise on low-dose CT degrades the measurement accuracy of the lung nodule volume. We compared the volumetric accuracy among deep-learning reconstruction (DLR), model-based iterative reconstruction (MBIR), and hybrid iterative reconstruction (HIR) at an ultra-low-dose setting. METHODS: Artificial ground-glass nodules (6 mm and 10 mm diameters, -660 HU) placed at the lung-apex and the middle-lung field in chest phantom were scanned by 320-row CT with the ultra-low-dose setting of 6.3 mAs. Each scan data set was reconstructed by DLR, MBIR, and HIR. The volumes of nodules were measured semi-automatically, and the absolute percent volumetric error (APEvol) was calculated. The APEvol provided by each reconstruction were compared by the Tukey-Kramer method. Inter- and intraobserver variabilities were evaluated by a Bland-Altman analysis with limits of agreements. RESULTS: DLR provided a lower APEvol compared to MBIR and HIR. The APEvol of DLR (1.36%) was significantly lower than those of the HIR (8.01%, p = 0.0022) and MBIR (7.30%, p = 0.0053) on a 10-mm-diameter middle-lung nodule. DLR showed narrower limits of agreement compared to MBIR and HIR in the inter- and intraobserver agreement of the volumetric measurement. CONCLUSIONS: DLR showed higher accuracy compared to MBIR and HIR for the volumetric measurement of artificial ground-glass nodules by ultra-low-dose CT. ADVANCES IN KNOWLEDGE: DLR with ultra-low-dose setting allows a reduction of dose exposure, maintaining accuracy for the volumetry of lung nodule, especially in patients which deserve a long-term follow-up.